KR102178353B1 - patch composition for diabetes mellitus and patch manufacturing method using the same - Google Patents

Abstract

The present invention relates to a diabetes treatment transdermal drug delivery patch composition in which insulin, corosolic acid, and herbal extracts are mixed, and a patch production method using the composition. A blood sugar improving agent, a transdermal drug delivery component, and a hydrogel composition that changes from a gel state to a sol state in response to the skin temperature are mixed. According to the present invention, insulin, corosolic acid, and herbal extract components can be continuously absorbed into skin without side effects.

Description

Transdermal drug delivery patch composition for diabetes treatment in which insulin, corosolic acid, and herbal extracts are mixed, and a patch manufacturing method using the composition {patch composition for diabetes mellitus and patch manufacturing method using the same}

In the present invention, when a hydrogel responsive to skin temperature changes to a sol state when used by being attached to the skin, the blood sugar improving agent mixed with liposomal insulin, corosolic acid, and herbal extracts is continuously eluted by a transdermal drug delivery component. The present invention relates to a transdermal drug delivery patch composition for treating diabetes, and a method of manufacturing a patch using the composition, which allows it to penetrate into the skin and thereby lower blood sugar levels to obtain a diabetes treatment effect.

In general, patches for skin adhesion have been used to relieve pain in body parts, heal wounds, or protect skin, and these methods are used in medicine, beauty, etc. due to the development of technology to develop patch materials and medicinal materials used for patches. Was used in various industrial fields, but its application range was very limited.

The skin adhesive patch is generally used in a therapeutic form for medicinal action on skin tissues or joints, or to increase the mobility of joints and muscles. The adhesive patch used for this purpose is formed by trapping a drug on one side in contact with the skin, and the drug's medicinal effect is transmitted through the skin or the joints and muscles are fixed by the physical force of the patch to affect mobility. Was formed.

In addition, conventional commercially available patches for skin adhesion do not have side effects caused by drugs that are administered orally, and deliver drugs through the skin into the body, so they maintain their medicinal efficacy or direct them to the skin in the treatment of people with gastrointestinal disorders. It was combined together as a treatment method. Typical examples of this are pars and smoking cessation patches.

On the other hand, some patients who have been administered oral hypoglycemic agents for a long period of 5 years or longer have poor blood sugar control even during treatment, and this is accompanied by side effects in patients with abnormal kidney or liver function. In this case, since it is no longer possible to control blood sugar with oral drugs, insulin injection therapy can be used together or switched.

However, in the case of insulin injection therapy, it is uncomfortable due to various problems such as hospitalization problems as the need to visit the hospital periodically to receive injections, and some patients stop insulin therapy due to the fear or pain of injections, or irregular insulin therapy is combined. There was a problem that the effect could not be obtained.

Accordingly, many types of preparations are being developed as a substitute for insulin injection. Among them, the patch type preparation is a system that delivers the drug through the skin, so the drug can consistently penetrate the skin and the drug effect can be continuously expressed. It is expected to be widely used because it can control the release rate of drugs and the rate of skin penetration.

As an example, a patch in which a diabetic treatment agent is applied to the endothelium to be absorbed by the skin is disclosed in Korean Patent Publication No. 1080203.

The above patent is to form an outer layer by preparing a solution in which a general polymer or biodegradable polymer is dissolved in a nanofiber sheet shape by an electrospinning method, and a solution in which a drug agent and a biodegradable polymer are dissolved in the upper layer of the outer layer is electrospinned. It is manufactured in a sheet shape to form an inner layer, and on the upper layer of the inner layer, a solution in which a biodegradable polymer or a patch-type polymer is dissolved in a physiologically active material is prepared in the form of a nanofiber sheet by electrospinning to form a second inner layer. Has been.

However, the above patent is only formed as a nanofiber sheet while spraying a solution, and the drug constituting the nanofiber sheet is sensitive to the skin temperature and cannot be continuously delivered for a long time.In particular, it is only described that the drug is used as a diabetes treatment agent. However, it is not possible to know what specific ingredients are.

On the other hand, insulin is a polymer material having a large particle size, and when applied or applied to the skin, it cannot easily penetrate and thus its absorption power is remarkably deteriorated, and thus the expected effect has not been exhibited. Because of this problem, insulin itself has not yet been applied to the patch.

Registered Patent Publication No. 10-1080203 (2011.10.31., Medical skin patch made of multi-layered nanofiber sheets) Publication Patent Publication No. 10-2016-0144107 (2016.12.16., Skin-attached bidirectional functional food patch containing nutrients absorbed through the skin) Registered Patent Publication No. 10-1004140 (2010.12.20., Method for manufacturing external skin preparation using hydrogel)

Accordingly, the applicant of the present invention conducted various studies to manufacture a patch that can be steadily absorbed into the skin for a long time without loss of a blood sugar improving agent when attached to the skin. As a result, a cold substance in the process of liposomeization by ultrasonic treatment of a blood sugar improving agent It was confirmed that the blood sugar improving agent was placed on the top and subjected to ultrasonic treatment, and during ultrasonic irradiation, it contracted rapidly after splitting and became liposome within a shorter time.

In addition, it was confirmed that when the composition of insulin, corosolic acid, and herbal extracts, mixed with licorice root and sukjihwang, can improve the blood sugar level and increase the diabetes treatment effect.

Therefore, it is to provide a transdermal drug delivery patch composition for the treatment of diabetes in which insulin, coronic acid, and herbal extracts are mixed.

The transdermal drug delivery patch composition for diabetes treatment in which insulin, corosolic acid, and herbal drug extract of the present invention are mixed to achieve the above object, is a hydrogel that changes from a gel state to a sol state in response to a blood sugar improving agent, a transdermal drug delivery component, and skin temperature. The composition is mixed, but the blood sugar improving agent is composed by mixing insulin, corosolic acid, and herbal medicine extract in a weight ratio of 8:1:1, and put on a cold substance in a state of being mixed with phospholipid in a weight ratio of 0.2-1:1. It is a blood sugar improving agent that has been placed and subjected to a liposomal process at intervals of 1 to 3 seconds for 2 to 30 minutes, and the herbal medicine extract is a mixture of licorice and galgeun and sukjihwang in a weight ratio of 5:3:2, respectively, and hot water extraction for 24 hours The transdermal drug delivery component is composed of polyacrylic acid having a PH concentration of 4.8 to 5.5 through a neutralization process, and 0.03 to 3% by weight of a liposomal blood sugar improving agent, and polyacrylic acid as a transdermal drug delivery component 45 to 55% by weight, and 0.4 to 2% by weight of agar as a hydrogel composition, 0.01 to 0.5% by weight of sodium hydroxide, 5 to 20% by weight of glycerin, 2 to 15% by weight of methylpropanediol, and sodium polyacrylate 0.3 to 1% by weight, aluminum glycinate 0.05 to 0.5% by weight, and the rest are mixed with purified water.

In addition, the method for producing a patch using the transdermal drug delivery patch composition for diabetes treatment in which insulin, corosolic acid, and herbal medicine extract of the present invention are mixed, is a mixture of licorice, galgeun, and sukjihwang at a weight ratio of 5:3:2, and hot water for 24 hours. The first step of extracting and obtaining herbal medicine extract: Insulin, corosolic acid, and herbal medicine extract are mixed in a weight ratio of 8:1:1 to form a blood sugar improving agent, and the thus prepared blood sugar improving agent is mixed with phospholipids and 0.2~1:1. A second step of forming a liposome target mixture by mixing in a weight ratio; A third step of placing the liposome target mixture mixed in the first step on top of a cold material including ice or dry ice; A fourth step of sonicating the mixture of liposomes on top of the cold material, so that insulin, corosolic acid, and herbal medicine extract are split into nanoparticles and surrounded by phospholipids to make liposomes; A fifth step of neutralizing the polyacrylic acid to undergo a neutralization process so that the PH concentration is 4.8 to 5.5; Liposomeized blood sugar improving agent 0.03 to 3% by weight, 45 to 55% by weight of polyacrylic acid that has undergone a neutralization process, 0.4 to 2% by weight of agar, 0.01 to 0.5% by weight of sodium hydroxide, and 5 to 20% by weight of glycerin , A sixth step of mixing 2 to 15% by weight of methylpropanediol, 0.3 to 1% by weight of sodium polyacrylate, 0.05 to 0.5% by weight of aluminum glycinate, and purified water to form a functional hydrogel composition; After applying the functional hydrogel composition formed through the above steps to the inner surface of nonwoven fabric and stretchable fabric with polyurethane bonded to the outer surface, heat curing at a temperature of 55 to 65°C for 60 to 80 hours to form a gel state, and then set Through the seventh step of cutting into shape; manufactured into a patch, and the functional hydrogel composition was heated to 100°C by adding polyacrylic acid to a stirrer and then adding purified water and sodium hydroxide, and adding agar to it. A first step of stirring by adding purified water; A second step of degassing after adding methylpropanediol, sodium polyacrylate, and liposomal blood sugar improving agent after the first step, stirring, and defoaming; After passing through the second process, aluminum glycinate is added and the stirred glycerin is added to a container, stirred, and then discharged from a stirrer to obtain a liquid functional hydrogel composition.

The transdermal drug delivery patch for diabetes treatment of the present invention made of the above composition is in response to skin temperature, and the gel-like hydrogel changes to a sol state, and liposomal insulin, corosolic acid, and herbal extracts (Moondong, Galgeun, Sukjihwang ) Is eluted and penetrated into the skin by the transdermal drug delivery component, thereby lowering the blood sugar level to provide an effect of improving blood sugar.Especially, even if it is used for a long time, insulin, corosolic acid, and herbal extract components are continuously used without side effects to the skin. It has the effect of dissolving and allowing it to be absorbed into the skin.

1 is a graph of the dissolution amount of a blood sugar improving agent eluted from a patch attached to the skin according to the present invention;
2 is a graph of daily blood glucose levels of the control group and the experimental group according to the present invention.

Hereinafter, a transdermal drug delivery patch composition for the treatment of diabetes in which insulin, corosolic acid, and herbal medicine extract are mixed according to the present invention, and a patch manufacturing method using the composition will be described in detail.

The transdermal drug delivery patch composition for diabetes treatment in which insulin and corosolic acid and herbal medicine extracts are mixed of the present invention is a hydrogel composition having a continuous absorption effect for a long time through the skin, and insulin and corosolic acid and herbal medicine extracts (macrosol, galgeun, sukjihwang) As an active ingredient, insulin, corosolic acid, and herbal extracts (Mulmundong, Galgeun, Sukjihwang) are continuously absorbed through the skin for a long time by simply attaching the patch without supplying insulin through the drug. Insulin lowers the blood sugar level while suppressing the increase in blood sugar levels.

Corosolic acid, which is added as an active ingredient, acts similar to insulin, absorbs glucose rapidly into cells and reduces blood sugar, thereby preventing diabetes, preventing tumor growth and proliferation, and blocking angiogenesis or metastasis. It is known to be effective.

Corosolic acid is contained in Banaba leaves by 2~3%, and increases the cell absorption rate in glucose by 45%, and in particular, acts to reduce triglycerides, which are the cause of diabetes, by 22% and cholesterol by 4.8%.

In addition, Macmundong, which is added as a herbal extract, uses the root as a perennial plant of the lily family.

Maekmundong strengthens the lungs, revitalizes the lungs, improves physical strength, and has an excellent effect in curing bronchitis such as cough and asthma. It is good for nutrient tonic and has an effect of lowering blood sugar levels.

In addition, Galgeun is a dried root of a vine plant of the leguminous family arrowroot (Pueraria montana var.lobata: Pueraria lobata) and dried roots after removing the pericarp, and its medicinal properties are persimmon, shin, and pyeong. ) And enters the bi (脾) and stomach (胃) and shows the efficacy of Haepyo (解表), Sujin (透疹), Saengjin (生津), and Jisa (止瀉). As pharmacological action, antipyretic action, blood pressure lowering action, memory enhancement, cerebral blood flow increase, coronary artery dilatation, heart function improvement, antiarrhythmic action, etc. have been reported (Kim Ho-cheol, Herbal Pharmacology, Jipmundang, 92-94, 2001).

Sukjihwang is a medicinal material that is steamed and dried from the roots of the perennial medicinal plant of the Hyeonsam family. It has a sweet but bitter taste and a warm nature to preserve blood and to preserve life. It is effective in treating symptoms of soreness, menstruation, dizziness, etc., and darkening the head by supplementing the substance). In addition, it is effective in tonicity, fever, weakness and congenital diseases.

In addition, Sukjihwang has a component called catanpol. This component prevents rapid rise in blood sugar and regulates blood sugar, as well as reinforcing blood vessel functions and smoothing blood flow.

The herbal extract is obtained by mixing Maekmundong, Galgeun and Sukjihwang in a weight ratio of 5:3:2, respectively, and hot water extraction for 24 hours.

In the present invention, when the corosolic acid and the herbal medicine extract are added together with insulin, the blood sugar level is suppressed from rising, and the blood sugar level is lowered together with insulin, thereby improving the blood sugar level by about 30% compared to simply reducing blood sugar by insulin. In addition, it is possible to achieve a more improved effect while using a smaller amount of insulin compared to the amount of conventional insulin used, thereby reducing the cost burden required for diabetes treatment.

The hydrogel composition is composed of a transdermal drug delivery component and a substance that changes from a gel state to a sol state in response to skin temperature. 45 to 55% by weight of polyacrylic acid as a transdermal drug delivery component, 0.4 to 2% by weight of agar as a hydrogel material, 0.01 to 0.5% by weight of sodium hydroxide, 5 to 20% by weight of glycerin, and 2 to 15 of methylpropanediol The composition is composed of a mixture of 0.3 to 1% by weight of sodium polyacrylate, 0.05 to 0.5% by weight of aluminum glycinate and the rest of purified water.

In addition, the blood sugar improving agent mixed as an active ingredient is composed by mixing insulin, corosolic acid, and herbal medicine extract at a weight ratio of 8:1:1, and this blood sugar improving agent is added to the hydrogel composition in an amount of 0.03 to 3% by weight. To form a gel composition.

If the blood sugar improving agent is added less than 0.03%, it is difficult to obtain the expected effect as the amount added is too small, and if it is added in excess of 3% by weight, the amount is too large to dissolve the hydrogel composition that is eluted in response to the skin temperature. Within time, all the blood sugar improving agents do not penetrate and remain, and a superior amount can be absorbed compared to the amount that should be absorbed, so it is more likely that problems such as palpitations and headaches may occur due to hypoglycemia.

At this time, since the insulin, corosolic acid, and herbal medicine extract are polymers having a relatively large particle size, there is a problem in that absorption through transdermal is not properly achieved. Therefore, for smooth absorption through transdermal, ultrasonic treatment is performed to mix the divided particles into nano-sized particles, and at this time, the divided particles are sonicated to form liposomes so that the divided particles do not merge again.

To this end, the blood glucose improving agent in which insulin, corosolic acid, and herbal extracts are mixed, is mixed with phospholipids in a weight ratio of 0.2 to 1: 1, and the insulin, corosolic acid, and herbal extracts are divided into nanoparticles through ultrasonic treatment. After being surrounded by phospholipids and not recombining, they are provided in a liposomeized state and separated from each other.

In the case of ultrasonic treatment, the ultrasonic treatment can be performed for 3 to 5 seconds at 1 to 3 second intervals for 2 to 30 minutes.

Here, in the case of performing the operation of liposomeization by irradiating ultrasonic waves on the mixed product of the blood sugar improving agent and phospholipid, the mixture of the blood sugar improving agent and phospholipid is placed on top of the cold substance and subjected to ultrasonic treatment, so that liposomes can be made in a short time. To be.

The functional hydrogel composition contains a nano-sized liposomal blood sugar improving agent (insulin + corosolic acid + herbal medicine extract), so when it is made as a patch and attached to the skin, the particles of the blood sugar improving agent are small as well as liposomes. It passes through the dermis and penetrates into the inner side and can be effectively absorbed, and thus, the absorption rate of the blood sugar improving agent is greatly increased, so that the expected effect can be exhibited.

Meanwhile, the polyacrylic acid is mixed with a pH concentration of 4.8 to 5.5 through a neutralization process.

The reason is that while the epidermis of the skin has weak acidity, polyacrylic acid is to have a PH concentration similar to that of the skin because polyacrylic acid has an acidic pH of about 2, and a significant amount of acidic polyacrylic acid is mixed. In this case, even if the skin temperature is sensitive and insulin, corosolic acid, and herbal extracts are eluted, the affinity with the skin decreases due to the difference in PH concentration, so that insulin cannot be effectively penetrated, as well as problems such as skin problems may occur.

Therefore, it is to increase the intimacy with the skin to enable effective penetration of insulin and to prevent the occurrence of skin troubles.

Looking at the process of manufacturing a patch using the liposomal insulin transdermal drug delivery patch composition for diabetes treatment as described above,

Insulin, corosolic acid, and herbal extracts are mixed in a weight ratio of 8:1:1 to form a blood sugar improving agent, and this blood sugar improving agent is mixed with phospholipids in a weight ratio of 0.2 to 1:1 to form a liposome target mixture. The target mixture is sonicated for 3 to 5 seconds at intervals of 1 to 3 seconds for 2 to 30 minutes, so that the blood sugar improving agent is divided into nano-sized particles and surrounded by phospholipids to form liposomes.

At this time, in the case of liposomeization by ultrasonic treatment, the liposome target mixture is placed on top of the cold material and sonicated.

The reason is that when the particles are split into nanoparticles through ultrasonic treatment and are liposomed by phospholipids, the particles that have been split into nano-sized particles are surrounded by phospholipids and are immediately contracted by cold substances in the process of making liposomes, and liposomes can be prepared within a shorter time. It can be completed, and accordingly, the effect of improving the production volume and production speed by 2 to 3 times or more compared to the conventional liposome operation is exhibited.

In addition, polyacrylic acid is added as a transdermal drug delivery component, and the polyacrylic acid has a pH concentration of 4.8 to 5.5 through a neutralization process.

To form a functional hydrogel composition, 0.03 to 3% by weight of a liposomal blood sugar improving agent is added to the stirrer, 45 to 55% by weight of polyacrylic acid, 0.4 to 2% by weight of agar as a hydrogel material, and 0.01 of sodium hydroxide Add ~0.5% by weight, 5 to 20% by weight of glycerin, 2 to 15% by weight of methylpropanediol, 0.3 to 1% by weight of sodium polyacrylate, 0.05 to 0.5% by weight of aluminum glycinate, and purified water Then, the mixture is mixed through a stirring process to form a functional hydrogel composition.

The composition process of the functional hydrogel composition in the above composition ratio consists of a total of three steps.

In the first step, after adding polyacrylic acid to a stirrer, purified water and sodium hydroxide are added, agar is added thereto, and purified water heated to 100°C is added and stirred.

In step 2, a liposomal blood sugar improving agent is added to a stirrer, methylpropanediol and sodium polyacrylate are added and stirred, followed by a defoaming process.

In step 3, aluminum glycinate is added and the stirred glycerin is added to a stirrer and stirred to form a functional hydrogel composition.

The functional hydrogel composition thus constituted is attached to the release film after applying the functional hydrogel composition to the inner surface of the nonwoven fabric and stretchable fabric to which the polyurethane is bonded to the outer surface.

As the polyurethane is bonded to the outer surface of the non-woven fabric, the functional hydrogel composition including the liposomal blood sugar improving agent is prevented from evaporating outward through the non-woven fabric, and at this time, the blood sugar improving agent is surrounded by phospholipids and is liposomed, so that it is transdermally In the process of penetration, insulin as well as corosolic acid and herbal extracts are penetrated without loss and can be absorbed as much as possible.

After passing through the above steps, in order to prepare a gel state, it is dried for 2 to 4 days at a temperature of 55 to 65°C, and then cut into a set shape and manufactured into a patch.

Hereinafter, the present invention will be described in more detail through examples and experimental examples. The following examples are merely illustrative of the present invention, and the scope of the present invention is not limited to the following examples.

[Example 1] Preparation of functional hydrogel patch

As shown in [Table 1] below, a functional hydrogel composition was formed by mixing a liposomal blood sugar improving agent (insulin + corosolic acid + herbal medicine extract) and a hydrogel material, and the blood sugar improving agent was mixed with phospholipids and then subjected to ultrasonic treatment. Divided into nano-sized liposomes was added.

Example 1 is a composition obtained by mixing a blood sugar improving agent (insulin + corosolic acid + herbal medicine extract), polycyclic acid, agar, sodium hydroxide, glycerin, methylpropanediol, sodium polyacrylate, aluminum glycinate, and purified water. 1 is a composition obtained by subtracting methylpropanediol from the Example and mixing only glycerin, Comparative Example 2 is a mixture of only methylpropanediol and removing glycerin from the Example, and Comparative Example 3 is a mixture of two components of glycerin and methylpropanediol in the Example. Butylene glycol was mixed without all, and Comparative Example 4 was obtained by subtracting all of the two components of glycerin and methylpropanediol in the Example and mixing propylene glycol.

Raw material name Content (% by weight) Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Example Blood sugar improving agent 0.05 0.05 0.05 0.05 0.05 Polyacrylic acid 49 49 49 49 49 Baby 0.88 0.88 0.88 0.88 0.88 Sodium hydroxide 0.1 0.1 0.1 0.1 0.1 glycerin 15 - - - 10 Methylpropanediol - 15 - - 5 Butylene Glycol - - 15 - - Propylene glycol - - - 15 - Sodium polyacrylate 0.7 0.7 0.7 0.7 0.7 Aluminum glycinate 0.2 0.2 0.2 0.2 0.2 Purified water 34.07 34.07 34.07 34.07 34.07 Sum 100 100 100 100 100

[Experimental Example 1] Blood glucose improving agent dissolution test

After filling the receptor compartment with physiological saline, preheat to 37°C, and then attach the sample prepared in the donor compartment to the skin collected from the hairless mouse, and use a blood sugar improving agent every 30 minutes. The elution amount was checked.

The dissolution test result can be confirmed in the graph of FIG. 1, and it was confirmed that the blood glucose improving agent was continuously eluted as time passed in both Comparative Examples 1 to 4 as well as Examples, and it was confirmed that 100% elution was reached in 120 minutes. there was.

As a result of the dissolution test every 30 minutes, it was confirmed that the initial elution amount was different depending on the solvent to be mixed, and the initial elution value was the highest when glycerin was used as the solvent, and the initial elution value was the lowest when methylpropanediol was used. In addition, when glycerin and methylpropanediol were used together, it was confirmed that the initial elution value was medium, but the elution amount was constant at 30 minute intervals.

Therefore, when using a mixture of glycerin and methylpropanediol, there is an effect that can be expected to be continuously absorbed into the skin in a uniform amount for a long time.

On the other hand, Figure 2 shows the blood glucose level when all of the insulin and corosolic acid and herbal extracts added as a blood sugar improving agent are added, and when only insulin and corosolic acid are added, and when only insulin is added without the addition of corosolic acid. A graph comparing blood glucose levels is shown.

[Experimental Example 2] Measurement of blood glucose level

[Table 2] below is an experimental group of mouse experiments. When insulin is added as a blood sugar improving agent (C), when corosolic acid is added (D), when insulin and corosolic acid are added (E), insulin and corosomal Four groups of sol acid and herbal extracts were added (F) as a diagram, and the control group was a normal mouse group (A) and a mouse group administered with alloxan monohydrate (B).

C D E F insulin ○ ○ ○ Corosolic acid ○ ○ ○ Herbal extract ○

A patch containing insulin, corosolic acid, insulin + corosolic acid, insulin + corosolic acid + herbal medicine extract was attached to the mice of the alloic acid-administered mouse group every day for 2 hours for 4 weeks, and blood glucose was measured and measured once a week. The results are shown in FIG. 2.

As shown in Figure 2, it was confirmed that the blood glucose levels of mice in all the experimental groups of C, D, E, and F were lowered, and the blood glucose levels of the mice attached with the insulin-containing patch were slightly higher than the corosolic acid-containing patch. It was confirmed that it was lowered.

In addition, it was confirmed that the blood glucose level of the patch containing insulin and corosolic acid was lowered by about 20% compared to the patch containing only insulin. In the case of the mouse with the patch containing insulin, corosolic acid and herbal extracts, insulin It was confirmed that the blood sugar level was lowered by about 30% compared to the patch containing gulf, and it was confirmed that there was a significant effect on improving blood sugar.

As described above, it was found that the patch containing insulin and corosolic acid and herbal extracts has a distinct hypoglycemic effect compared to the patch containing either insulin or corosolic acid alone or with insulin or corosolic acid.

Claims (2)

A blood sugar improving agent, a transdermal drug delivery component, and a hydrogel composition that changes from a gel state to a sol state in response to the skin temperature are mixed,
The blood sugar improving agent is composed of insulin, corosolic acid, and herbal extracts mixed in a weight ratio of 8:1:1, and put on a cold material in a mixture with phospholipids in a weight ratio of 0.2 to 1:1 for 2 to 30 minutes. It is a blood sugar improving agent that is liposomeized through ultrasonic treatment every 1 to 3 seconds during the period.
The herbal medicine extract is an extract obtained by hot water extraction for 24 hours by mixing Macmundong, Galgeun and Sukjihwang at a weight ratio of 5:3:2, respectively,
The transdermal drug delivery component is composed of polyacrylic acid having a PH concentration of 4.8 to 5.5 through a neutralization process,
0.03 to 3% by weight of a liposomal blood sugar improving agent, 45 to 55% by weight of polyacrylic acid as a transdermal drug delivery component, 0.4 to 2% by weight of agar as a hydrogel composition, 0.01 to 0.5% by weight of sodium hydroxide, and glycerin 5 It is characterized in that the composition is formed by mixing ~20% by weight, 2 to 15% by weight of methylpropanediol, 0.3 to 1% by weight of sodium polyacrylate, 0.05 to 0.5% by weight of aluminum glycinate, and the rest of purified water. Transdermal drug delivery patch composition for diabetes treatment in which insulin, corosolic acid, and herbal extracts are mixed.
The first step of obtaining a herbal medicine extract by mixing Maekmundong, Galgeun, and Sukjihwang in a weight ratio of 5:3:2 and extracting with hot water for 24 hours:
Insulin, corosolic acid, and herbal extracts are mixed in a weight ratio of 8:1:1 to form a blood sugar improving agent, and the prepared blood sugar improving agent is mixed with phospholipids in a weight ratio of 0.2-1:1 to form a liposome target mixture. The second step;
A third step of placing the liposome target mixture mixed in the first step on top of a cold material including ice or dry ice;
A fourth step of sonicating the mixture of liposomes on top of the cold material, so that insulin, corosolic acid, and herbal medicine extract are split into nanoparticles and surrounded by phospholipids to make liposomes;
A fifth step of neutralizing the polyacrylic acid to undergo a neutralization process so that the PH concentration is 4.8 to 5.5;
Liposomeized blood sugar improving agent 0.03 to 3% by weight, 45 to 55% by weight of polyacrylic acid that has undergone a neutralization process, 0.4 to 2% by weight of agar, 0.01 to 0.5% by weight of sodium hydroxide, and 5 to 20% by weight of glycerin , A sixth step of mixing 2 to 15% by weight of methylpropanediol, 0.3 to 1% by weight of sodium polyacrylate, 0.05 to 0.5% by weight of aluminum glycinate, and purified water to form a functional hydrogel composition;
After applying the functional hydrogel composition formed through the above steps to the inner surface of nonwoven fabric and stretchable fabric with polyurethane bonded to the outer surface, heat curing at a temperature of 55 to 65°C for 60 to 80 hours to form a gel state, and then set Through the seventh step of cutting into a shape; manufactured into a patch,
The functional hydrogel composition includes: a first step of adding polyacrylic acid to a stirrer and then adding purified water and sodium hydroxide, and then adding agar to the purified water heated to 100°C and stirring;
A second step of degassing after adding methylpropanediol, sodium polyacrylate, and liposomal blood sugar improving agent after the first step, stirring, and defoaming;
After passing through the second process, aluminum glycinate is added to the agitated glycerin in a container, stirred, and then discharged from the stirrer to obtain a liquid functional hydrogel composition. A method for producing a patch using a transdermal drug delivery patch composition for diabetes treatment in which insulin, corosolic acid, and herbal extracts are mixed.

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